Mononuclear phagocytes (monocytes and macrophages) are critical components of both innate and acquired immunity and are found in virtually every tissue of the body, including the central nervous system. Mononuclear phagocytes participate in both antibody dependent and independent cytotoxicity, phagocytosis and killing of bacteria, destruction of effete erythrocytes, presentation of antigens for T cell activation, and secretion of a wide variety of inflammatory cytokines.
The secretion of inflammatory cytokines, as well as mononuclear phagocyte effector functions, are greatly influenced by soluble mediators. For example, priming by interferon gamma (IFNγ) and exposure to lipopolysaccharide, tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), or granulocyte-macrophage colony stimulating factor (GM-CSF) can stimulate mononuclear phagocytes to secrete inflammatory cytokines such as TNFα, IL-1 and interleukin-6 (IL-6) (Auger, M. J. and J. A. Ross. 1992. In: The Macrophage: the natural Immune System, New York: Oxford University Press, pp. 1-74). Interleulkin-10 (IL-10; originally knows as cytokine synthession inhibitory factor) has been shown to inhibit the expression of a wide range of inflammatory cytokines in vitro (Berkman, N. et al. 1995. J. Immunol. 155:4412–4418; de Waal Malefyt, R. et al. 1991. J. Exp. Med. 174:1209–1220) as well as in vivo (Chernoff, A. E. et al. 1995. J. Immunol. 154:5492–5499; van der Poll, T. et al. 1997. J. Immunol. 158:1971–1975). Glucocorticoids, interleukin-4 (IL—4) and interleukin-13 (IL13) have also been shown to down regulate the expression of inflammatory cytokines produced by mononuclear phagocytes. In addition to inhibiting the release of inflammatory cytokines, glucocorticoids have also been shown to upregulate the expression of CD163 on mononuclear phagocytes (Hogger, P. et al. 1998. Pharm. Res. 15:296–302; Hogger, P. et al. 1998. J. Immunol. 161:1883–1890; Wenzel, I. et al. 1996. Eur. J. Immunol. 26:2758–2763).
CD163 is a mononuclear phagocyte restricted antigen which is a member of the cysteine rich scavenger receptor family group B. Normal human macrophages stain brightly for CD163 and glucocorticoid treatment in vivo increases CD163 expression (Zwadlo-Klarwasser, G. et al. 1992. Int. Arch. Allergy Immunol. 97:178–180; Zwadlo-Klarwasser, G. et al. 1990. Int. Arch. Allergy Immunol. 91:175–180). It has been suggested that these CD163 bright macrophages may play a role in the resolution of inflammation as they are found in high numbers in inflamed tissues (Zwadlo, G. et al. 1987. Exp. Cell Biol. 55:295–304) and have been shown to release an incompletely characterized anti-inflammatory mediator (Zwadlo-Klarwasser, G. et al. 1995. Int. Arch. Allergy Immunol. 107:430–431).
One mononuclear phagocyte marker that bears a striking resemblance to CD163 is p155 (Morganelli, P. et al. 1988. J. Immunol. 140:2296–2304). Expression of this 134 kDa (non-reduced)/155 kDa (reduced) glycoprotein is restricted to mononuclear phagocytes and upregulated by glucocorticoid treatment. It has now been found that CD163 is identical to P155 and that this molecule could have activity as an anti-inflammatory molecule. Thus, this glycoprotein is believed to be useful as a biomarker for inflammation and inflammatory conditions and processes in humans.
A method has now been developed for detection of CD163 in human plasma. This method is useful in monitoring inflammation and inflammatory processes in humans.